Since the 1940's penicillins have played an important role in the chemotherapy of infectious disease. Much research has been done and many derivatives of penicillins have been prepared. A number of penicillins have shown sufficient antibacterial activity to be commercialized. This large amount of research in all commercial products have been directed to penicillins which contain the 7-oxo-1-aza-4-thiabicyclo[3.2.0]heptane nucleus. Work on the total synthesis of penicillins has also been studied by various investigators but this work also has been directed to preparing compounds with the same 1-aza-4-thiabicycloheptane nucleus.
A small amount of research has been conducted in an attempt to prepare penicillins with an unnatural nucleus. Examples of these include systems without the .alpha.-methyl groups or in which the sulfur atom is at a different position in the ring system. One unsuccessful attempt at preparing the 7-oxo-3-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid system has been reported in the literature; J. Chem. Soc.(C), 188 (1971). The trivial name for this bicyclic nucleus has been recently proposed as isopenicillin, Can. J. Chem., 55, 468 (1977).
We now wish to report the successful synthesis of compounds containing the isopenicillin nucleus. These compounds are prepared by a total synthetic method, and have antibacterial activity.